A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the Uni...

Descripción completa

Detalles Bibliográficos
Autores principales: Seviiri, Mathias, Law, Matthew H., Ong, Jue-Sheng, Gharahkhani, Puya, Fontanillas, Pierre, Olsen, Catherine M., Whiteman, David C., MacGregor, Stuart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9741635/
https://www.ncbi.nlm.nih.gov/pubmed/36496446
http://dx.doi.org/10.1038/s41467-022-35345-8
_version_ 1784848367947350016
author Seviiri, Mathias
Law, Matthew H.
Ong, Jue-Sheng
Gharahkhani, Puya
Fontanillas, Pierre
Olsen, Catherine M.
Whiteman, David C.
MacGregor, Stuart
author_facet Seviiri, Mathias
Law, Matthew H.
Ong, Jue-Sheng
Gharahkhani, Puya
Fontanillas, Pierre
Olsen, Catherine M.
Whiteman, David C.
MacGregor, Stuart
author_sort Seviiri, Mathias
collection PubMed
description Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.
format Online
Article
Text
id pubmed-9741635
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-97416352022-12-12 A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma Seviiri, Mathias Law, Matthew H. Ong, Jue-Sheng Gharahkhani, Puya Fontanillas, Pierre Olsen, Catherine M. Whiteman, David C. MacGregor, Stuart Nat Commun Article Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees. Nature Publishing Group UK 2022-12-10 /pmc/articles/PMC9741635/ /pubmed/36496446 http://dx.doi.org/10.1038/s41467-022-35345-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Seviiri, Mathias
Law, Matthew H.
Ong, Jue-Sheng
Gharahkhani, Puya
Fontanillas, Pierre
Olsen, Catherine M.
Whiteman, David C.
MacGregor, Stuart
A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title_full A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title_fullStr A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title_full_unstemmed A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title_short A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
title_sort multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9741635/
https://www.ncbi.nlm.nih.gov/pubmed/36496446
http://dx.doi.org/10.1038/s41467-022-35345-8
work_keys_str_mv AT seviirimathias amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT lawmatthewh amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT ongjuesheng amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT gharahkhanipuya amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT fontanillaspierre amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT olsencatherinem amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT whitemandavidc amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT macgregorstuart amultiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT seviirimathias multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT lawmatthewh multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT ongjuesheng multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT gharahkhanipuya multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT fontanillaspierre multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT olsencatherinem multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT whitemandavidc multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma
AT macgregorstuart multiphenotypeanalysisreveals19susceptibilitylociforbasalcellcarcinomaand15forsquamouscellcarcinoma

Ejemplares similares